No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in organotypic rat hippocampal cultures

Marie-Louise Sveen; Gitte M Knudsen; Susana Aznar

doi:10.1016/j.neulet.2004.01.051

No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in organotypic rat hippocampal cultures

Marie-Louise Sveen, Gitte M Knudsen, Susana Aznar

Abstrakt

MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with highest affinity for the first. Whether 5-HT2A receptor density decreases due to MDMA's direct effect on postsynaptic serotonin receptors is at present not known. This study analyzes whether direct stimulation of the postsynaptic 5-HT2A receptor by MDMA in organotypic hippocampal cultures results in cell death and downregulation of this receptor. Fifty or 100 microM MDMA was added to 1 week old cultures, made of 11 day old rat pups. Fluorojade and immunostaining for MAP2 and 5-HT2A to determine neurodegeneration, and changes in receptor density, respectively, resulted in no significant differences. MDMA's neurotoxicity and regulation of post-synaptic 5-HT2A receptors thus seems to require the presence of intact serotonergic terminals.

Originalsprog	Engelsk
Tidsskrift	Neuroscience Letters
Vol/bind	362
Udgave nummer	1
Sider (fra-til)	6-9
Antal sider	4
ISSN	0304-3940
DOI	https://doi.org/10.1016/j.neulet.2004.01.051
Status	Udgivet - 13 maj 2004

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10.1016/j.neulet.2004.01.051

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@article{f253ae07ae434103b3a5cc1917e4a9b2,

title = "No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in organotypic rat hippocampal cultures",

abstract = "MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with highest affinity for the first. Whether 5-HT2A receptor density decreases due to MDMA's direct effect on postsynaptic serotonin receptors is at present not known. This study analyzes whether direct stimulation of the postsynaptic 5-HT2A receptor by MDMA in organotypic hippocampal cultures results in cell death and downregulation of this receptor. Fifty or 100 microM MDMA was added to 1 week old cultures, made of 11 day old rat pups. Fluorojade and immunostaining for MAP2 and 5-HT2A to determine neurodegeneration, and changes in receptor density, respectively, resulted in no significant differences. MDMA's neurotoxicity and regulation of post-synaptic 5-HT2A receptors thus seems to require the presence of intact serotonergic terminals.",

keywords = "Animals, Cell Count/methods, Cell Death/drug effects, Hippocampus/chemistry, N-Methyl-3,4-methylenedioxyamphetamine/pharmacology, Organ Culture Techniques, Rats, Receptor, Serotonin, 5-HT2A/analysis",

author = "Marie-Louise Sveen and Knudsen, {Gitte M} and Susana Aznar",

year = "2004",

month = may,

day = "13",

doi = "10.1016/j.neulet.2004.01.051",

language = "English",

volume = "362",

pages = "6--9",

journal = "Neuroscience Letters",

issn = "0304-3940",

publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in organotypic rat hippocampal cultures

AU - Sveen, Marie-Louise

AU - Knudsen, Gitte M

AU - Aznar, Susana

PY - 2004/5/13

Y1 - 2004/5/13

N2 - MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with highest affinity for the first. Whether 5-HT2A receptor density decreases due to MDMA's direct effect on postsynaptic serotonin receptors is at present not known. This study analyzes whether direct stimulation of the postsynaptic 5-HT2A receptor by MDMA in organotypic hippocampal cultures results in cell death and downregulation of this receptor. Fifty or 100 microM MDMA was added to 1 week old cultures, made of 11 day old rat pups. Fluorojade and immunostaining for MAP2 and 5-HT2A to determine neurodegeneration, and changes in receptor density, respectively, resulted in no significant differences. MDMA's neurotoxicity and regulation of post-synaptic 5-HT2A receptors thus seems to require the presence of intact serotonergic terminals.

AB - MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with highest affinity for the first. Whether 5-HT2A receptor density decreases due to MDMA's direct effect on postsynaptic serotonin receptors is at present not known. This study analyzes whether direct stimulation of the postsynaptic 5-HT2A receptor by MDMA in organotypic hippocampal cultures results in cell death and downregulation of this receptor. Fifty or 100 microM MDMA was added to 1 week old cultures, made of 11 day old rat pups. Fluorojade and immunostaining for MAP2 and 5-HT2A to determine neurodegeneration, and changes in receptor density, respectively, resulted in no significant differences. MDMA's neurotoxicity and regulation of post-synaptic 5-HT2A receptors thus seems to require the presence of intact serotonergic terminals.

KW - Animals

KW - Cell Count/methods

KW - Cell Death/drug effects

KW - Hippocampus/chemistry

KW - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology

KW - Organ Culture Techniques

KW - Rats

KW - Receptor, Serotonin, 5-HT2A/analysis

U2 - 10.1016/j.neulet.2004.01.051

DO - 10.1016/j.neulet.2004.01.051

M3 - Journal article

C2 - 15147768

VL - 362

SP - 6

EP - 9

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 1

ER -

No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in organotypic rat hippocampal cultures

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